Minor Groove Orientation of the KWKK Peptide Tethered via the N-Terminal Amine to the Acrolein-Derived 1,N2-γ-Hydroxypropanodeoxyguanosine Lesion with a Trimethylene Linkage,
Year: 2010
Type: article
Abstract: DNA-protein conjugates are potentially repaired via proteolytic digestion to DNA-peptide conjugates. The latter have been modeled with the amino-terminal lysine of the peptide KWKK conjugated via a trimethylene linkage to the N(2)-dG amine positioned in 5'-d(GCTAGCXAGTCC)-3'.5'-d(GGACTCGCTAGC)-3' (X = N(2)-dG-trimethylene link-KWKK). This linkage is a surrogate for the reversible linkage formed by the gamma-OH-1,N(2)-propanodeoxyguanosine (gamma-OH-PdG) adduct. This conjugated KWKK stabilizes the DNA. Amino acids K(26), W(27), K(28), and K(29) are in the minor groove. The W(27) indolyl group does not intercalate into the DNA. The G(7) N(2) amine and the K(26) N-terminal amine nitrogens are in the trans configuration with respect to the C(alpha) or C(gamma) of the trimethylene tether, respectively. The structure of this DNA-KWKK conjugate is discussed in the context of its biological processing.
Source: Biochemistry
DOI: 10.1021/bi100364f
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: hybrid
Estimated APC paid: $4,500
Awards: Cellular responses to DNA-protein crosslinks, G3421439927, Novel Targets in Cancer Chemotherapy: Chemical Biology of Guanine Alkylation, Center in Molecular Toxicology, G6209630593, BASE FLIPPING AND DNA DAMAGE RECOGNITION, Chemistry and Biology of Carcinogen-DNA Adducts, Discovery and development of OGG1 activators as precision drugs for modification of Alzheimer's disease progression., T4 Endonuclease V Structure-Function Analysis, 500 MHZ NUCLEAR MAGNETIC RESONANCE SPECTROMETER, G9000089795, Cancer Center Support Grant
OpenAlex ID: W2012855934